Study of abnormal plasma low-density lipoprotein in rhesus monkeys with diet-induced hyperlipidemia

Abstract
Male rhesus monkeys were divided into 3 groups: 5 were fed a regular primate chow diet and were used as controls; 4 received an average American diet; and 5 a special low-fat primate chow diet supplemented with 25% coconut oil and 2% cholesterol. In all of these animals, the plasma low-density lipoproteins (LDL) were isolated by ultracentrifugal flotation between densities of 1.019 and 1.050 g/ml. The LDL of the 5 control monkeys had variable MWs, with a mean value of 3.12 .+-. 0.21 .times. 106 (range: 2.92 .times. 106-3.45 .times. 106), and an average partial specific volume of 0.969 .+-. 0.003 ml/g; both were assessed by flotation equilibrium analysis in the analytical ultracentrifuge. In the individual animals, however, the physical properties of LDL were invariant with time. The administration of either an average American diet or a coconut oil-cholesterol diet was accompanied by hypercholesterolemia associated with changes in LDL which were characterized by increases in MW to 3.52 .+-. 0.21 .times. 106 (average of 9 monkeys) and in partial specific volume to 0.973 .+-. 0.002 ml/g. These changes were particularly evident when the MW of LDL from monkeys in the normolipidemic state was compared with that obtained from the same monkeys during the hyperlipidemic state. Chemical analyses revealed that the particles from the hyperlipidemic animals had a relatively higher cholesteryl ester content, a slight increase in phospholipids and a marked decrease to nearly complete absence of triglycerides. The other lipoprotein components, protein, carbohydrate, free cholesterol and fatty acids, did not vary significantly from those of control LDL. The administration of atherogenic diets probably causes structural changes in LDL which appear to be accounted for, at least in part, by changes in the composition of the lipid moiety. The changes in physical and chemical properties noted in the LDL of rhesus monkeys with experimentally induced hypercholesterolemia contrast with the apparent structurally normal LDL from rhesus monkeys with spontaneous hypercholesterolemia.